p130Cas: A key signalling node in health and disease
Abstract
p130Cas/breast cancer anti-oestrogen resistance 1 (BCAR1) is a member of the Cas (Crk-associated substrate) family of adaptor proteins, which have emerged as key signalling nodes capable of interactions with multiple proteins, with important regulatory roles in normal and pathological cell function. The Cas family of proteins is characterised by the presence of multiple conserved motifs for protein-protein interactions, and by extensive tyrosine and serine phosphorylations. Recent studies show that p130Cas contributes to migration, cell cycle control and apoptosis. p130Cas is essential during early embryogenesis, with a critical role in cardiovascular development. Furthermore, p130Cas has been reported to be involved in the development and progression of several human cancers. p130Cas is able to perform roles in multiple processes due to its capacity to regulate a diverse array of signalling pathways, transducing signals from growth factor receptor tyrosine kinases, non-receptor tyrosine kinases, and integrins. In this review we summarise the current understanding of the structure, function, and regulation of p130Cas, and discuss the importance of p130Cas in both physiological and pathophysiological settings, with a focus on the cardiovascular system and cancer.
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Little is currently known about CASS4 biology or its role in neurological health and disease.
“Despite CASS4 being increasingly linked to AD risk in humans (EADB et al., 2026; Lambert et al., 2013; Lin et al., 2017; Ramos de Matos et al., 2018; Schwartzentruber et al., 2021; Wang et al., 2015b), little is currently known about CASS4 biology or its role in neurological health and disease.”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Barrett et al., 2013
PTK2B encodes the protein PYK2 and is a suggested CASS4-binding partner.
“Moreover, mutations in the focal adhesion gene PTK2B , which encodes the protein PYK2 and is a suggested CASS4binding partner (Barrett et al., 2013; Beck et al., 2014), have also been linked to increased AD risk in GWAS studies (Lambert et al., 2013; Lin et al., 2017; Ramos de Matos et al., 2018; Schwartzentruber et al., 2021; Wang et al., 2015b).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Barrett et al., 2013
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Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members
Deneka, A., Korben, V. A., & Golemis, E. A. (2015) · Gene · doi:10.1016/j.gene.2015.06.062 · Cited by 33 · see citing works
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Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis
Walsh, A. E., Davis, B. A., Samuels, J. D., Mills, W. A., Thanos, J. M., Johnson, A. M., Moore, K. A., Puchalski, M. A., Steacy, E. J., Wendell, B. W., et al. (2026) · Journal of Experimental Medicine · doi:10.1084/jem.20260104
- Authors
- Barrett, A., Pellet-Many, C., Zachary, I. C., Evans, I. M., & Frankel, P.
- Affiliations
- University College London (GB)
- Corresponding author
- Barrett, Angela
- Frankel, Paul
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 25
- Issue
- 4
- Pages
- 766-777
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W2126859572
- Cited by
- 93
- References
- 5
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 13 · 2014: 10 · 2013: 2
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Signalling (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- British Heart Foundation (RG/11/11/29050, RG/06/003/21131)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- p130Cas, adaptor proteins, protein-protein interaction, tyrosine phosphorylation, serine phosphorylation, cell migration, cell cycle regulation, apoptosis, embryonic development, cardiovascular development, tumor progression, growth factor receptor tyrosine kinases, non-receptor tyrosine kinase, integrins, signal transduction
- MeSH terms
- Cardiovascular System, Humans, Neoplasms, Phosphorylation, Signal Transduction, Guanine Nucleotide Exchange Factors, Mechanotransduction, Cellular, Crk-Associated Substrate Protein
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